CA2191454A1 - Phosphinic acid derivatives and their use as endothelin converting enzyme inhibitors - Google Patents

Phosphinic acid derivatives and their use as endothelin converting enzyme inhibitors

Info

Publication number
CA2191454A1
CA2191454A1 CA002191454A CA2191454A CA2191454A1 CA 2191454 A1 CA2191454 A1 CA 2191454A1 CA 002191454 A CA002191454 A CA 002191454A CA 2191454 A CA2191454 A CA 2191454A CA 2191454 A1 CA2191454 A1 CA 2191454A1
Authority
CA
Canada
Prior art keywords
alkyl
cycloalkyl ring
alpha
acid derivatives
converting enzyme
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002191454A
Other languages
French (fr)
Other versions
CA2191454C (en
Inventor
Brian A. Mckittrick
Michael F. Czarniecki
Samuel Chackalamannil
Shin Chung
Shawn Defrees
Andrew W. Stamford
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Corp
Original Assignee
Brian A. Mckittrick
Michael F. Czarniecki
Samuel Chackalamannil
Shin Chung
Shawn Defrees
Andrew W. Stamford
Schering Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Brian A. Mckittrick, Michael F. Czarniecki, Samuel Chackalamannil, Shin Chung, Shawn Defrees, Andrew W. Stamford, Schering Corporation filed Critical Brian A. Mckittrick
Publication of CA2191454A1 publication Critical patent/CA2191454A1/en
Application granted granted Critical
Publication of CA2191454C publication Critical patent/CA2191454C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/303—Cycloaliphatic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems

Abstract

Phosphinic acid derivatives of structural formula (I) or a pharmaceutically acceptable salt thereof, wherein R is H, alkyl or alkanoyloxymethylene; R1, R2, R3 and R4 are H, alkyl, alkenyl, alkenylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, carboxyalkyl, thioalkyl, alkoxythioalkyl, aminoalkyl, alkylaminoalkyl, cycloalkyl-substituted alkyl or heterocycloalkyl; or R1 and R2 form a cycloalkyl ring of 3-8 members and R3 and R4 are as defined; or R3 and R4 form a cycloalkyl ring of 3-7 members and R1 and R2 are as defined; or R1 and R2 together, and R3 and R4 together, each form a cycloalkyl ring; R5 is -OR9 or -NHR9, wherein R9 is hydrogen or alkyl;
n is 0 or 1; A1 is p-aminobenzoyl or p-aminobenzenesulfonyl, or A1 and R5 together form a radical of an .alpha.-aminoacyl derivative; and R6 is phenylmethoxycarbonyl, arylcarbonyl, heteroarylcarbonyl or -A2-R7, wherein A2 is a divalent .alpha.-iminoacyl radical, and R7 is a substituent on the .alpha.-imino atom selected from H, R8OCO-, R8SO2- and R8NHCO-, wherein R8 is aryl, arylmethyl or (C1-C8)alkyl; are disclosed for use as endothelin converting enzyme inhibitors; also disclosed are a genus of novel compounds wherein R3 and R4 form a cycloalkyl ring, and pharmaceutical compositions comprising said novel compounds.
CA002191454A 1994-06-29 1995-06-19 Phosphinic acid derivatives and their use as endothelin converting enzyme inhibitors Expired - Fee Related CA2191454C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/267,630 1994-06-29
US08/267,630 US5476847A (en) 1994-06-29 1994-06-29 Derivatives of phosphinic acid useful as endothelin converting enzyme inhibitors
PCT/US1995/007128 WO1996000732A1 (en) 1994-06-29 1995-06-19 Phosphinic acid derivatives

Publications (2)

Publication Number Publication Date
CA2191454A1 true CA2191454A1 (en) 1996-01-11
CA2191454C CA2191454C (en) 2007-01-02

Family

ID=23019568

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002191454A Expired - Fee Related CA2191454C (en) 1994-06-29 1995-06-19 Phosphinic acid derivatives and their use as endothelin converting enzyme inhibitors

Country Status (13)

Country Link
US (1) US5476847A (en)
EP (1) EP0767794B1 (en)
JP (1) JP3833704B2 (en)
AT (1) ATE189455T1 (en)
AU (1) AU2901395A (en)
CA (1) CA2191454C (en)
DE (1) DE69514919T2 (en)
DK (1) DK0767794T3 (en)
ES (1) ES2144131T3 (en)
GR (1) GR3032918T3 (en)
MX (1) MX9606523A (en)
PT (1) PT767794E (en)
WO (1) WO1996000732A1 (en)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1276710B1 (en) * 1995-06-14 1997-11-03 Zambon Spa DERIVATIVES OF PHOSPHINIC ACID WITH METALLOPEPTIDASE INHIBITIVE ACTIVITY
US5958905A (en) * 1996-03-26 1999-09-28 Texas Biotechnology Corporation Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin
MC2441A1 (en) * 1997-07-31 1998-03-11 Exsymol Sa Cosmetic composition useful in particular for bleaching the skin and melanogenesis inhibiting agent comprising such a cosmetic composition
FR2834989B1 (en) * 2002-01-18 2005-05-20 Commissariat Energie Atomique PHOSPHINIC PSEUDO-PEPTIDE DERIVATIVES SELECTIVELY INHIBITING THE C-TERMINAL ACTIVE SITE OF THE ANGIOTENSIN I CONVERSION ENZYME (ACE)
FR2882752B1 (en) * 2005-03-01 2007-05-04 Servier Lab NOVEL PHOSPHINIC AMINOACIDIC DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US10821132B2 (en) 2007-02-26 2020-11-03 Heartbeet Ltd Compositions of nitrates and methods of use thereof
US11759477B2 (en) 2007-02-26 2023-09-19 Heartbeet Ltd. Compositions of nitrates and methods of use thereof
CA2678093C (en) 2007-02-26 2017-10-24 Jon Lundberg Performance enhancing composition and use thereof
US10842813B2 (en) 2007-02-26 2020-11-24 Heartbeet Ltd Compositions of nitrates and methods of use thereof
FR2934267B1 (en) 2008-07-23 2010-08-13 Pharmaleads AMINOPHOSPHINIC DERIVATIVES USEFUL IN THE TREATMENT OF PAIN
PE20120878A1 (en) 2009-04-01 2012-08-06 Genentech Inc ANTI-FcRH5 ANTIBODIES AND IMMUNOCONJUGATES

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4374131A (en) * 1981-04-27 1983-02-15 E. R. Squibb & Sons, Inc. Amino and substituted amino phosphinyl-alkanoyl compounds
US4716155A (en) * 1981-12-24 1987-12-29 E. R. Squibb & Sons, Inc. Phosphorus containing compounds and hypotensive use thereof
US4452791A (en) * 1982-03-15 1984-06-05 E. R. Squibb & Sons, Inc. Aminoalkyl and related substituted phosphinic acid angiotensin converting enzyme inhibitors
US4661473A (en) * 1984-03-27 1987-04-28 Merck & Co., Inc. Renin inhibitors containing peptide isosteres
EP0210545A3 (en) * 1985-07-24 1988-07-20 Merck & Co. Inc. Phosphorous containing enzyme inhibitors
EP0209848A3 (en) * 1985-07-24 1988-07-27 Merck & Co. Inc. Enzyme inhibitors
CA1290097C (en) * 1985-07-24 1991-10-01 Merck & Co., Inc. Peptide enzyme inhibitors
ZW23187A1 (en) * 1986-12-15 1988-06-29 Hoffmann La Roche Phosphinic acid derivatives
IL89900A0 (en) * 1988-04-12 1989-12-15 Merck & Co Inc Hiv protease inhibitors useful for the treatment of aids and pharmaceutical compositions containing them
GB9006855D0 (en) * 1990-03-27 1990-05-23 Ferguson Ltd Method of producing a printed circuit board
EP0569487A1 (en) * 1991-01-31 1993-11-18 Abbott Laboratories Endothelin converting enzyme inhibitors
AU6491294A (en) * 1993-03-26 1994-10-24 Warner-Lambert Company Inhibitors of endothelin converting enzyme

Also Published As

Publication number Publication date
WO1996000732A1 (en) 1996-01-11
AU2901395A (en) 1996-01-25
MX9606523A (en) 1997-12-31
CA2191454C (en) 2007-01-02
GR3032918T3 (en) 2000-07-31
EP0767794B1 (en) 2000-02-02
DE69514919D1 (en) 2000-03-09
DK0767794T3 (en) 2000-07-24
JP3833704B2 (en) 2006-10-18
JPH10502081A (en) 1998-02-24
EP0767794A1 (en) 1997-04-16
ATE189455T1 (en) 2000-02-15
US5476847A (en) 1995-12-19
DE69514919T2 (en) 2000-06-29
ES2144131T3 (en) 2000-06-01
PT767794E (en) 2000-06-30

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